期刊
MOLECULAR THERAPY
卷 16, 期 12, 页码 2022-2029出版社
CELL PRESS
DOI: 10.1038/mt.2008.196
关键词
-
资金
- Swim Across America
- National Institutes of Health (NIH) [CA33049, CA59350, CA10260]
- William H. and Alice Goodwin
- Commonwealth Foundation for Cancer Research
- Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center (MSKCC)
- Translational and Integrative Medicine Research Fund (MSKCC)
- Damon Runyon-Lilly Clinical Investigator Award
Granulocte-macrophage colony-stimulating factor (GM-CSF) enhances immune response by inducing proliferation, maturation, and migration of dentric cells (DCs) as well as expansion and differentiation of B and T lymphocytes. The potency of DNA vaccines can be enhaced by the addition of DNA encoding cytokines, acting as molecular adjuvants. We conducted a phase I/II trial of human GM-CSF DNA in conjunction with a multipeptide vaccine (gp 100 and tyrosine) in stage III/IV melanoma patients. Nineteen human leukocyte antigen (HLA)-A*0201(+) patients were treated. Three dose levels were studied: 100, 400, and 800 mu g DNA/injection, administered subcutneously every month with 500 mu g of each peptide. In the dose-ranging study, three patients were treated at each dose level. The remaining patients were then treated at the highest dose. Most toxicities were grade 1 injection-site reactions. Eight patients (42%) developed CD8(+) T-cell response, defined by a >= 3 SD increase in baseline reactivity to tyrosine or gp 100 peptide in tetramer or intracellular cytokine staining (ICS) assays. There was no relationship between dose and T-cell response. Responding T cells had an effector memory cell phenotype. Polyfunctional T cells were also demonstrated. At a median of 31 months follow-up, median survival has not been reached. Human GM-CSF DNA was found to be a safe adjuvant.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据